How Circadian Disruption Leads to Adverse Health Effects

University of Massachusetts Amherst researchers report that internal misalignment, a state of desynchrony between and within organs that occurs during jet lag or shift work, causes an adverse impact on neurogenesis as well as some of the other adverse health effects caused by circadian disruption.

“Circadian disruption impacts a lot of things,” explains Michael Seifu Bahiru, lead author of the paper published in eNeuro. “There are links to cancer, diabetes, and hypertension, as well as adverse impacts on neurogenesis.”

Until recently, the researchers have faced a sort of chicken-or-egg question. “We always wondered what actually is the root cause of the ailments from circadian disruption?” Bahiru says. “Does the problem come from the act of shifting or the shift itself?”

To test their hypothesis, the team studied cell birth and differentiation in Syrian hamsters with a recessive mutation in the circadian clock gene Cryptochrome 1 (Cry 1) gene that speeds up the clock in constant conditions and dramatically accelerates its ability to shift in response to light. Senior author Eric Bittman named the mutation, discovered in previous research, duper. The research team also tested a control group of hamsters without the duper mutation. Both underwent the same sequence of changes in the light cycle.

They simulated jet lag in the form of eight-hour advances and delays at eight 16-day intervals. A cell birth marker was given in the middle of the experiment. Results showed that jet lag has little effect on cell birth but steers the fate of newborn cells away from becoming neurons. Dupers are immune to this effect of phase shifts. “As predicted, the duper animals re-entrained quicker, but also were resistant to the negative effects of the jet lag protocol, whereas the control—the wild type hamsters—had reduced neurogenesis,” Bahiju says. 

“The findings indicate that circadian misalignment is critical in jet lag,” the paper concludes. 

The ultimate goal of Bittman’s lab is to advance understanding of the pathways involved in human biological clocks, which could lead to the prevention of or treatment for the effects of jet lag, shift work, and circadian rhythm disorders. This latest research is a next step toward that goal.